Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein

doi:10.2174/1871520617666170803155025

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	Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein
	Liu, Zulong 1,3; Zhu, Hengrui 3; Qu, Shijin; Tang, Lisha 3; Cao, Lihuan 3; Yu, Wenbo 3; Yang, Xianmei 3; Jiang, Songmin 3; Zhu, Dayuan 2; Tan, Changheng2
刊名	ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
	2018
卷号	18 期号:2 页码:286-294
关键词	Aglaia perviridis multi-drug resistance KB/VCR cells P-gp reversal agent pyramidatine
ISSN号	1871-5206
DOI	10.2174/1871520617666170803155025
文献子类	Article
英文摘要	Background: Multi-drug resistance (MDR) remains a major impediment in cancer therapy. A major goal for scientists is to discover more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects. Objective: In the present study, we aim to determine the anti-MDR effects of pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, on KB/VCR (vincristine-resistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells. Methods: Cell viability and average resistant fold (RF) of Z88 were examined by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry, western blot, RT-PCR, Rhodamine 123 accumulation assay and P-glycoprotein (P-gp) ATPase assay were used to demonstrate the anti-MDR activity and mechanism of Z88. Results: The average RF of Z88 is 0.09 and 0.51 in KB/VCR and MCF-7/ADR cells. A CCK-8 assay showed that Z88 could enhance the cytotoxicity of VCR toward KB/VCR cells. A FACS analysis revealed that Z88 could enhance the VCR-induced apoptosis as well as G2/M arrest in a dose-dependent manner in KB/VCR cells. Western blot results showed that the expression levels of PARP, Bax, and cyclin B1 all increased after treatment with 0.2 mu mol/L (mu M) of VCR combined with 10 mu M of Z88 for 24 h in KB/VCR cells. Z88 also could enhance the accumulation of rhodamine 123. Further studies showed that Z88 could inhibit the verapamil stimulated P-gp ATPase activity. Additionally, qPCR detection and western blot assays revealed that Z88 could decrease the expression of P-gp at both RNA and protein level. Conclusion: Z88 exerted potent anti-MDR activity in vitro and its mechanisms are associated with dual-inhibition of the function and expression of P-gp. These findings encourage efforts to develop more effective reversal agents to circumvent MDR based on Z88.
资助项目	Scientific Research Innovation Project of Shanghai Education Commission[14YZ062] ; National Science Foundation of China[81402515] ; China Postdoctoral Science Foundation[2012T50395] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2009ZX09301-001]
WOS关键词	MEDIATED MULTIDRUG-RESISTANCE ; MOLECULAR-MECHANISMS ; BREAST-CANCER ; APOPTOSIS ; GP ; TRANSPORTER ; DOXORUBICIN ; REVERSAL ; MDR ; EXPRESSION
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000430724600012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272314]
专题	天然药物化学研究室
通讯作者	Tan, Changheng; Yu, Long
作者单位	1.Shanghai Univ Tradit Chinese Med, Liver Dis Res Inst, Shuguang Hosp, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Nat Med Chem, Shanghai 201203, Peoples R China 3.Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Zulong,Zhu, Hengrui,Qu, Shijin,et al. Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein[J]. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY,2018,18(2):286-294.
APA	Liu, Zulong.,Zhu, Hengrui.,Qu, Shijin.,Tang, Lisha.,Cao, Lihuan.,...&Yu, Long.(2018).Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein.ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY,18(2),286-294.
MLA	Liu, Zulong,et al."Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein".ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY 18.2(2018):286-294.